While infliximab and etanercept are designed to block the biological activities of TNFa, these agents are sufficiently different in their structure that they may have distinct, as well as overlapping, mechanisms of action. The clearest evidence of this possibility can be inferred from their differential activities in certain diseases such as Crohn's disease in which infliximab, but not etanercept, shows beneficial therapeutic activity. The mechanism of their differential biological activities is not known. That infliximab and etanercept show differential activities in other diseases suggests that they may also have distinct effects in RA.